Hormonal therapy, also known as androgen deprivation therapy (ADT), is a cornerstone in the management of prostate cancer. This treatment strategy focuses on reducing or blocking the action of male hormones (androgens) that fuel the growth of prostate cancer cells. There are several types of hormonal agents used in prostate cancer management, each with its own benefits and challenges.

Types of Hormonal Therapies

  1. Luteinizing Hormone-Releasing Hormone (LHRH) Agonists and Antagonists: LHRH agonists, such as leuprolide (Lupron) and goserelin (Zoladex), initially increase testosterone levels before significantly lowering them, a phenomenon known as “flare.” To counteract this, anti-androgens are often prescribed concurrently. LHRH antagonists, like degarelix (Firmagon) and relugolix (Orgovyx), lower testosterone levels without causing flare, making them a preferred choice for some patients​ (Mayo Clinic)​​ (CancerInfo)​.
  2. Anti-Androgens: These drugs, including bicalutamide (Casodex) and enzalutamide (Xtandi), block androgens from binding to their receptors on prostate cancer cells. Anti-androgens are often used in combination with LHRH agonists to enhance the overall effectiveness of hormone therapy​ (Mayo Clinic)​​ (CancerInfo)​.
  3. CYP17 Inhibitors: Abiraterone (Zytiga) is a CYP17 inhibitor that blocks the production of androgens from all sources, including the adrenal glands and the tumor itself. It is used in combination with prednisone to treat metastatic castration-resistant prostate cancer (mCRPC)​ (Comprehensive Cancer Information)​​ (CancerInfo)​.
  4. Orchiectomy: This surgical procedure involves the removal of the testicles, thereby drastically reducing testosterone levels. Although effective, it is often considered less desirable due to its permanent and psychologically impactful nature​ (Mayo Clinic)​.

Benefits and Effectiveness

Hormonal therapies are particularly effective in reducing the size of prostate tumors and slowing disease progression. For instance, relugolix has shown a significant reduction in testosterone levels compared to traditional treatments like leuprolide, with fewer cardiovascular side effects, making it a safer option for patients with pre-existing heart conditions​ (Comprehensive Cancer Information)​.

Combination therapies, such as pairing an LHRH agonist with an anti-androgen, have been found to enhance treatment efficacy and improve survival rates. For high-risk patients, new hormonal agents (NHAs) used in neoadjuvant settings (before surgery) can reduce the risk of recurrence and improve long-term outcomes​ (UroToday)​​ (JWatch)​.

Challenges and Side Effects

Despite their benefits, hormonal therapies are associated with several side effects that can impact the quality of life. Common side effects include:

  • Loss of libido and erectile dysfunction
  • Bone thinning (osteoporosis)
  • Hot flashes
  • Increased risk of diabetes and cardiovascular diseases
  • Fatigue and weight gain​ (Mayo Clinic)​​ (CancerInfo)​.

To mitigate these side effects, intermittent hormone therapy is sometimes used, where treatment is given for a period and then stopped until it is needed again. This approach can help reduce side effects without significantly compromising the effectiveness of the therapy​ (Mayo Clinic)​.

Future Directions and Research

Ongoing research is focused on improving the effectiveness of hormonal therapies while minimizing side effects. Studies like the EvoPAR-Prostate01 trial are exploring combinations of PARP inhibitors with new hormonal agents to delay disease progression and the initiation of chemotherapy in patients with metastatic castration-sensitive prostate cancer (mCSPC)​ (UroToday)​.

Furthermore, advances in personalized medicine are paving the way for more tailored treatment plans based on genetic and molecular profiling of individual tumors. This approach aims to optimize the efficacy of hormonal therapies and improve patient outcomes​ (JWatch)​.


References

  1. American Cancer Society. “Hormone Therapy for Prostate Cancer.”
  2. Mayo Clinic. “Hormone therapy for prostate cancer.”
  3. National Cancer Institute. “FDA Approves Relugolix for Advanced Prostate Cancer.”
  4. UroToday. “AUA 2024: EvoPAR-Prostate01: Phase III, Double-Blind, Placebo-Controlled, 2-Cohort, Randomized Study of Saruparib (AZD5305) in Combination with New Hormonal Agents in Patients with mCSPC +/- HRR Mutations.”